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https://www.readbyqxmd.com/read/29054871/engineering-the-enantioselectivity-and-thermostability-of-a-%C3%AE-lactamase-from-microbacterium-hydrocarbonoxydans-for-the-kinetic-resolution-of-vince-lactam
#1
Shuaihua Gao, Shaozhou Zhu, Rong Huang, Hongxia Li, Hao Wang, Guojun Zheng
To produce promising biocatalysts, natural enzymes often need to be engineered to increase their catalytic performance. In this study, the enantioselectivity and thermostability of a (+)-γ-lactamase from Microbacterium hydrocarbonoxydans as the catalyst in the kinetic resolution of Vince lactam were improved. Enantiomerically pure (-)-Vince lactam is the key synthon in the synthesis of antiviral drugs such as carbovir and abacavir, which are used to fight against human HIV and hepatitis B viruses. The work was initialized by using the combinatorial active-site saturation test strategy to engineer the enantioselectivity of the enzyme...
October 20, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29054515/blood-transfusion-management-and-transfusion-related-outcomes-in-daratumumab-treated-patients-with-relapsed-or-refractory-multiple-myeloma
#2
Ajai Chari, Suzanne Arinsburg, Sundar Jagannath, Toshihisa Satta, Ivey Treadwell, Donna Catamero, Gillian Morgan, Huaibao Feng, Clarissa Uhlar, Imran Khan, Parul Doshi, Saad Usmani
INTRODUCTION: Daratumumab, a human CD38 monoclonal antibody approved for multiple myeloma (MM) treatment, binds red blood cells (RBCs), resulting in panagglutination in compatibility tests. Published mitigation methods avoid additional testing, ensuring timely release of blood products. Blood transfusion management and transfusion-related outcomes of daratumumab-treated patients in the SIRIUS study are reported, with emphasis on 2 clinical sites. PATIENTS AND METHODS: Patients had MM treated with ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were refractory to a proteasome inhibitor and an immunomodulatory drug...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29053912/community-based-screening-of-hepatitis-c-with-a-one-step-rna-detection-algorithm-from-dried-blood-spots-analysis-of-key-populations-in-barcelona-spain
#3
V Saludes, C Folch, A Morales-Carmona, L Ferrer, L Fernández, R Muñoz, M Jiménez, E Loureiro, P Fernández-Dávila, E Bascuñana, J Casabona, E Martró
Alternative strategies are required to enhance the diagnosis of silent hepatitis C virus (HCV) infections in hard-to-reach key populations at risk. Among them, HCV prevalence and bio-behavioural data is scarce for HIV-negative men who have sex with men (MSM) and men and trans-women sex workers. We sought to describe and assess the potential benefits of a community-based one-step HCV screening and confirmatory strategy for these populations in Barcelona. The screening strategy based on a real-time RT-PCR assay for HCV-RNA detection in dried-blood spots (DBS) was validated and implemented in addition to an antibody point-of-care test in a community centre...
October 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29053257/orthogonal-screening-of-anti-cancer-drugs-using-an-open-access-microfluidic-tissue-array-system
#4
Dongguo Lin, Peiwen Li, Jinqiong Lin, Bowen Shu, Weixin Wang, Qiong Zhang, Na Yang, Dayu Liu, Banglao Xu
Screening for potential drug combinations presents significant challenges to the current microfluidic cell culture systems, due to the requirement of flexibility in liquid handling. To overcome this limitation, we present here an open-access microfluidic tissue array system specifically designed for drug combination screening. The microfluidic chip features a key structure in which a nanoporous membrane is sandwiched by a cell culture chamber array layer and a corresponded media reservoir array layer. The microfluidic approach takes advantage of the characteristics of the nanoporous membrane: on one side, this membrane permits the flow of air but not liquid, thus acting as a flow-stop valve to enable automatic cell distribution; on the other side, it allows diffusion-based media exchange and thus, mimics the endothelial layer...
October 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29052968/non-steroidal-estrogen-receptor-isoform-selective-biphenyls
#5
Seema Bhatnagar, Anjali Soni, Swati Kaushik, Megha Rikhi, T R Santhosh Kumar, B Jayaram
Estrogen receptor (ER) has been a therapeutic target to treat ER positive breast cancer, most notably by agents known as selective estrogen receptor modulators (SERMs). However, resistance and severe adverse effects of known drugs gave impetus to the search for newer agents with better therapeutic profile. ERα and ERβ are two isoforms sharing 56% identity, and having different physiological functions and expressions in various tissues. Only two residues differ in the active sites of the two isoforms motivating us to design isoform selective ligands...
October 20, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29052384/-research-progress-of-serum-pharmacochemistry-of-traditional-chinese-medicine
#6
REVIEW
Fei-Xiang Ma, Pei-Feng Xue, Yuan-Yuan Wang, Yi-Nuo Wang, Shu-Yuan Xue
Serum pharmacochemistry of traditional Chinese medicine(TCM) is an effective method to rapidly screen the effective substances and reveal the compatibility law of compound by identification and analysis of constituents migrating to blood after oral administration. In the last two decades, it has been universally accepted and widely applied in the field. With the cross-fusion with other disciplines, such as serum pharmacology, pharmacokinetics, metabolomics, network pharmacology and systems biology, serum pharmacochemistry shows comprehensive superiority in explaining drug changes in vivo and in vitro, interactions between drugs, interactions between drug and body, which coincides with the complexity of TCM compatibility, multi-components, multi-targets and multi-mechanisms...
April 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29050798/animals-anxiety-and-anxiety-disorders-how-to-measure-anxiety-in-rodents-and-why
#7
REVIEW
Jaanus Harro
Measurement of anxiety is desirable for the benefit of drug development and understanding the brain function and mental well-being. Animal models offer the advantages of detailed neurobiological analysis, experimental manipulation of specific components in the brain circuits that underlie psychopathology, and the possibility of screening novel drugs with clinical potential. A large variety of animal models of anxiety and screening tests of anxiolytics is currently in use. While their value in advancing the knowledge and predicting therapeutic success of drugs is unquestionable, the expectations have grown much higher, and the frustration over absence of novel successful drug concepts is rising...
October 16, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29050757/ionophore-a23187-shows-anti-tuberculosis-activity-and-synergy-with-tebipenem
#8
Wei Huang, Julien Briffotaux, Xinwei Wang, Lili Liu, Pei Hao, Mena Cimino, Maria Virginia Buchieri, Amine Namouchi, Jose-Antonio Ainsa, Brigitte Gicquel
The objective of this study was to find molecules with anti-mycobacterial activity from a natural compounds library, investigate their mechanisms of resistance, and assess their synergy with antibiotics. We screened a library of 2582 natural compounds with Mycobacterium aurum with the aim of identifying molecules with anti-mycobacterial activity. The hits with the lowest MICs in M. aurum were also tested for their antimicrobial activity in other mycobacterial species including M. tuberculosis complex strains...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29050130/-evaluation-of-a-high-intensity-fluorescent-fluorophage-method-for-diagnosis-of-drug-resistance-in-tuberculosis
#9
J J Luo, X Yu, Y F Ma, L P Zhao, Y Y Shang, Y Y Fu, H R Huang
Objective: To evaluate the high-intensity green fluorescent protein fluorophage Φ(2)GFP10 method for drug susceptibility testing of tuberculosis for isoniazid(INH), rifampin(RIF), and streptomycin(SM). Methods: A total of 128 clinical M. tuberculosis strains were isolated from patients with suspected drug-resistant tuberculosis visiting Beijing Chest Hospital (Beijing, China) from April to June 2014.All of the isolates were tested by the phage assay, while conventional drug susceptibility tests were performing on Lwenstein-Jensen culture medium as reference...
October 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29048876/microchemical-plant-in-a-liquid-droplet-plasmonic-liquid-marble-for-sequential-reactions-and-attomole-detection-of-toxin-at-microliter-scale
#10
Xuemei Han, Charlynn Sher Lin Koh, Hiang Kwee Lee, Wee Shern Chew, Xing Yi Ling
Miniaturizing the continuous multi-step operations of a factory into a microchemical plant offers a safe and cost-effective approach to promote high-throughput screening in drug development and enforcement of industrial/environment safety. While particle-assembled microdroplets in the form of liquid marble are ideal as microchemical plant, these platforms are mainly restricted to single-step reactions and limited to ex-situ reaction monitoring. Herein, we utilize plasmonic liquid marble (PLM), formed by encapsulating liquid droplet with Ag nanocubes, to address these issues and demonstrate it as an ideal microchemical plant to conduct reaction-and-detection sequences on-demand in a non-disruptive manner...
October 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#11
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29046464/screening-for-neuraminidase-inhibitor-resistance-markers-among-avian-influenza-viruses-of-the-n4-n5-n6-and-n8-neuraminidase-subtypes
#12
Won-Suk Choi, Ju Hwan Jeong, Jin Jung Kwon, Su Jeong Ahn, Khristine Kaith S Lloren, Hyeok-Il Kwon, Hee Bok Chae, Jungwon Hwang, Myung Hee Kim, Chul-Joong Kim, Richard J Webby, Elena A Govorkova, Young Ki Choi, Yun Hee Baek, Min-Suk Song
Several subtypes of avian influenza viruses (AIVs) are emerging as novel human pathogens, and the frequency of related infections has increased in recent years. Although neuraminidase (NA) inhibitors (NAIs) are the only class of antiviral drugs available for therapeutic intervention for AIV-infected patients, studies on NAI resistance among AIVs have been limited and markers of resistance are poorly understood. Previously, we identified unique NAI-resistance substitutions in AIVs of N3, N7, and N9 NA subtypes...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29045762/synthesis-determination-of-the-lipophilicity-anticonvulsant-activity-and-preliminary-safety-of-new-derivatives-of-n-4-arylpiperazin-1-yl-alkyl-pyrrolidine-2-5-dione
#13
Sabina Rybka, Jolanta Obniska, Paweł Żmudzki, Paulina Koczurkiewicz, Katarzyna Wójcik-Pszczoła, Elżbieta Pękala, Adrian Bryła, Anna Rapacz
A new series of derivatives of 1,3-substituted pyrrolidine-2,5-dione as potential anticonvulsant agents are described in this paper. Initial pharmacological screening for these compounds was performed using acute models of seizures (MES and scPTZ tests) in mice after intraperitoneal administration. A quantitative pharmacological research revealed that the most promising compound were N-[{4-(3-trifluoromethylphenyl)-piperazin-1-yl}-propyl]-3-benzhydryl-pyrrolidine-2,5-dione monohydrochloride (11) with ED50=75...
October 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29045302/neurosteroid-levels-in-patients-with-bipolar-disorder-and-a-history-of-cannabis-use-disorders
#14
Brittany L Mason, Erin Van Enkevort, Francesca Filbey, Christine E Marx, John Park, Alyson Nakamura, Prabha Sunderajan, E Sherwood Brown
PURPOSE/BACKGROUND: In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs). METHODS/PROCEDURES: Bipolar depressed participants were enrolled in a randomized placebo-controlled clinical trial to evaluate the efficacy of add-on pregnenolone for depression and before receiving pregnenolone or placebo...
October 17, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29044549/effects-of-clioquinol-on-the-scuticociliatosis-causing-protozoan-miamiensis-avidus-in-olive-flounder-paralichthys-olivaceus
#15
J-H Lee, J-J Park, J-H Choi, S-Y Kang, Y-J Kang, K H Park
Scuticociliatosis is a devastating and intractable protozoal disease in olive flounder, leading to a significant loss throughout the year. This study aimed to investigate a systemically effective antiscuticociliatosis agent for olive flounder for better absorption into the infected internal organs. The in vitro and in vivo antiscuticociliatosis effects of clioquinol (CQ) were examined after screening 30 biocidal agents against the highly pathogenic scuticociliate Miamiensis avidus. CQ was the most potent in vitro drug of those tested against cultured M...
October 17, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29043602/fluorinated-pyrrole-incorporated-2-thiazolyl-hydrazone-motifs-a-new-class-of-antimicrobial-and-anti-tuberculosis-agents
#16
P V Sowmya, Boja Poojary, Vasantha Kumar, U Vishwanatha, Premalatha Shetty
In aim of obtaining novel bio-active compounds, a new series of fluorinated 1-(4-(aryl)thiazol-2-yl)-2-((1-(aryl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)hydrazines (5a-t) and 1-(4-(4-aryl)thiazol-2-yl)-2-((3-(2,4-dichlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazines (8a-d) were synthesized and screened for their antibacterial and antifungal activities. The potent compounds were further screened in vitro for anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Compounds 5a, 5c-5h and 5m were found to be good inhibitors of B...
October 17, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29042372/awareness-and-willingness-towards-pre-exposure-prophylaxis-against-hiv-infection-among-individuals-seeking-voluntary-counselling-and-testing-for-hiv-in-taiwan-a-cross-sectional-questionnaire-survey
#17
Yi-Chieh Lee, Sui-Yuan Chang, Kuan-Yin Lin, Lan-Hsin Chang, Wen-Chun Liu, Cheng-Hsin Wu, Hsin-Yun Sun, Chien-Ching Hung, Shan-Chwen Chang
OBJECTIVES: We aimed to investigate the awareness and willingness towards pre-exposure prophylaxis (PrEP) among individuals seeking voluntary counselling and testing (VCT) for HIV in Taiwan, where PrEP is currently not reimbursed by the insurance. METHODS: Between April and October 2016, a questionnaire interview was conducted among VCT clients to inquire about the attitudes towards PrEP against HIV infection. Multivariate logistic regression analysis was performed to identify the associated factors with willingness to initiate PrEP...
October 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/29042260/pldt-planarian-light-dark-test-an-invertebrate-assay-to-quantify-defensive-responding-and-study-anxiety-like-effects
#18
Ashenafi Mebratu Zewde, Frances Yu, Sunil Nayak, Christopher Tallarida, Allen B Reitz, Lynn G Kirby, Scott M Rawls
BACKGROUND: Planarians, like rodents, instinctively spend more time in dark versus light environments when given a choice. This behavioral phenomenon is called negative phototaxis, which may reflect defensive responding related to an anxiety-like phenotype. NEW METHOD: We propose a planarian light/dark test, designated PLDT, to predict anxiogenic- or anxiolytic-like effects. Experimentally, we placed a planarian at the midline of a Petri dish, containing test compound or water, that was split evenly into light and dark compartments and determined time spent in the light over 10min...
October 14, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29041938/development-of-breath-test-for-pneumoconiosis-a-case-control-study
#19
Hsiao-Yu Yang, Ruei-Hao Shie, Che-Jui Chang, Pau-Chung Chen
BACKGROUND: Lipid peroxidation plays an important role in the pathogenesis of pneumoconiosis. Volatile organic compounds (VOCs) generated from lipid peroxidation might be used to detect pneumoconiosis. The objective of this study was to develop a breath test for pneumoconiosis. METHODS: A case-control study was designed. Breath and ambient air were analysed by gas chromatography/mass spectrometry. After blank correction to prevent contamination from ambient air, we used canonical discriminant analysis (CDA) to assess the discrimination accuracy and principal component analysis (PCA) to generate a prediction score...
October 17, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29041901/prevalence-of-drug-resistant-pulmonary-tuberculosis-in-india-systematic-review-and-meta-analysis
#20
Vishal Goyal, Vijay Kadam, Prashant Narang, Vikram Singh
BACKGROUND: Drug-resistant pulmonary tuberculosis (DR-TB) is a significant public health issue that considerably deters the ongoing TB control efforts in India. The purpose of this review was to investigate the prevalence of DR-TB and understand the regional variation in resistance pattern across India from 1995 to 2015, based on a large body of published epidemiological studies. METHODS: A systematic review of published studies reporting prevalence of DR-TB from biomedical databases (PubMed and IndMed) was conducted...
October 17, 2017: BMC Public Health
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